Candida albicans is a pathogenic yeast fungus which can cause severe and resistant to treatment infections in mammals, for example, moniliasis of the mouth. Infections (candidiasis) caused by Candida albicans, are extremely resistant to treatment but, under normal conditions, rarely fatal. On the other hand, Candida albicans is an opportunistic and dangerous organism should it infect persons having comprised immune systems such as, for example, AIDS patients and cancer patients undergoing chemotherapy. Under such circumstances, an infection by Candida albicans can become quite fatal. Prior to this invention, the principal and, substantially only, treatment of choice for Candida albicans has been the drug amphotericin-B. As well known in the art, treatment with amphotericin-B has a great many disadvantages causing numerous and, quite serious, adverse side effects. In humans, the side effects include, under varying conditions, fever, anorexia, nausea and vomiting, diarrhea, muscle and joint pain, phlebitis and thiophlebitis, anemia, abnormal renal function, anuria, cardiovascular distress, hypertension and hypotension.
There has been a continuing search and extensive efforts made to discover a new and clinically useful agent against Candida albicans which may be used as an alternative to amphotericin-B. In accordance with the invention, it has been discovered that the compound onychine, and therapeutic compositions comprising onychine, has remarkable anticandidal activity.
The discovery and extraction of eupolauridine from the tree found throughout West Africa, and its possibly remarkable anticandidal properties, was reported in the Journal of Natural Products, Vol. 50, No. 5, pp. 961-964, Sept.-Oct. 1987, by Hufford, Shihchih Liu, Clark and Babajide Oguntimein.
During the synthesis of eupolauridine, the intermediate compound onychine was discovered to be an effective treatment against Candida albicans. Treatment against Candida albicans utilizing the drug of the invention may be by any of the conventional routes of administration, for example, oral, intramuscular, intravenous, or rectally. Onychine is preferably administered in combination with a pharmaceutically-acceptable carrier which may be solid or liquid, dependent upon choice and route of administration. Examples of acceptable carriers include, but are not limited to, starch, dextrose, sucrose, lactose, gelatin, agar, stearic acid, magnesium stearate, acacia, and similar carriers. Examples of liquids include water, edible oils, e.g. peanut and corn.
When administered in solid form, onychine and a diluent carrier may be in the form of tablets, capsules, powders, lozenges, suppositories prepared by any of the well known methods. When given as a liquid preparation, the mixture of active compound and liquid diluent carrier may be in the form of a suspension administered as such. Onychine is administered in a non-toxic dosage concentration sufficient to inhibit the growth and/or destroy the Candida albicans organism. The actual dosage unit will be determined by such generally recognized factors as body weight of the patient and/or severity and type of pathological condition the patient might be suffering with prior to becoming infected with the Candida albicans organism. With these considerations in mind, the dosage of a particular patient can be readily determined by the medical practitioner in accordance with the techniques known in the medical arts.